Guidance on Novel Influenza A/H1N1 in Solid Organ Transplant Recipients

Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS. Novel influenza A/H1N1 virus has caused significant illness worldwide. In response to this global crisis, the American Society of Transplantation (AST) Infectious Diseases Community of Practice and the Transplant Infectious Diseases section of The Transplantation Society (TTS) developed a guidance document for novel H1N1. In this paper, we discuss current guidance for H1N1 as it relates to solid organ transplantation. We include discussion around clinical presentation, diagnosis, therapy and prevention specifically addressing areas such as chemoprophylaxis, immunization and donor-derived infection. Although this document addresses conditions specific to novel H1N1, many principles could be applied to future pandemics. As new information emerges about novel H1N1, updates will be made to the electronic version of the document posted on the websites of the AST and TTS. Officially endorsed by the American Society of Transplantation (AST), The Transplantation Society (TTS) and the Canadian Society of Transplantation (CST) Influenza A and B are common causes of viral infections each year in transplant recipients, with predictable complications including viral pneumonia, secondary bacterial pneumonia and possibly acute allograft rejection in the setting of weaning of immunosuppression (1Vilchez RA McCurry K Dauber J et al.Influenza virus infection in adult solid organ transplant recipients.Am J Transplant. 2002; 2: 287-291Crossref PubMed Scopus (202) Google Scholar). Annual vaccination with seasonal trivalent influenza vaccine for recipients as well as close contacts is the standard of care in most transplant centers. In April 2009, a novel influenza A (H1N1) virus was initially detected in two children in the United States and subsequently determined to be the cause of outbreaks of disease in Mexico; within 2 months, infection had spread worldwide, causing the World Health Organization (WHO) to declare a pandemic on June 11, 2009. Infection has been noted to be most common in the young, with particularly severe disease in pregnancy and presumably in more traditional high-risk groups for influenza infection, including transplant candidates and recipients. Although initially effective against this novel H1N1 strain, oseltamivir resistance was noted in two immunocompromised patients in August 2009 (2Centers for Disease Control and Prevention. Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients – Seattle,Washington, 2009. Morbid Mortal Wkly Rept/MMWR 2009; 58: 1–4, August 14, 2009.Google Scholar). Reassortment with seasonal human influenza A strains and potentially with H5N1, with unpredictable virulence is a significant concern. Recent data show that in persons born before 1950, there is a potential for cross-reactive antibodies to novel H1N1 in 34% (3Hancock K Veguilla V Lu X et al.Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus.N Engl J Med. 2009; (Sept 10. [Epub ahead of print].)Crossref Scopus (1103) Google Scholar). Reaction to this novel respiratory virus in the transplant community has been swift, with concern for prevention, diagnosis and treatment of infection as public health data mount and the course of the pandemic evolves. The International Society for Heart and Lung Transplantation has developed guidelines for heart and lung transplant recipients in the pandemic setting, raising concern for transmission of novel H1N1 infection from thoracic organ donors (4Danziger-Isakov LA Husain S Mooney ML Hannan MM for the ISHLT infectious diseases councilThe Novel 2009 H1N1 Influenza Virus Pandemic: Unique considerations for programs in cardiothoracic transplantation.J Heart Lung Transplant. 2009; (Oct 21 [Epub ahead of print].)Abstract Full Text Full Text PDF Scopus (37) Google Scholar). Animal and human autopsy studies have demonstrated that acute influenza A infection in the immunocompetent host may result in infection of multiple organs, including the brain, kidney, pancreas, spleen, liver and heart, in addition to the lungs (5Frankova V Jirasek A Tumova B Type A influenza: Postmortem virus isolations from different organs in human lethal cases.Arch Virol. 1977; 53: 265-268Crossref PubMed Scopus (53) Google Scholar, 6Fislova T Gocnik M Sladkova T et al.Multiorgan distribution of human influenza A virus strains observed in a mouse model.Arch Virol. 2009; 154: 409-419Crossref PubMed Scopus (60) Google Scholar, 7Kuiken T Rimmelzwaan GF Van Amerongen G Osteohaus AD. Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis).Vet Pathol. 2003; 40: 304-310Crossref PubMed Scopus (109) Google Scholar, 8Korteweg C Gu J Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans.Am J Pathol. 2008; 172: 1155-1170Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar). This has implications for potential donor transmission for transplant types other than lung. Overall, the impact of infection in potential donors (living and deceased), in those waiting on the transplant list with endstage organ disease, and in those having undergone transplantation has implications for donor selection, peritransplant management and the care of the transplant recipient. The Infectious Diseases Community of Practice of AST and the Transplant Infectious Disease section of The Transplantation Society have developed the following guidelines for the prevention, diagnosis and treatment of novel H1N1 influenza A infection in the solid organ transplant (SOT) setting, using available data on current patterns of infection, reports of resistance, and what is already known about the control of influenza. The guidelines will be updated as new data become available. Updates will be posted on the AST and TTS websites. •H1N1 should be suspected when patients present with flu-like symptoms (i.e. temperature ≥37.8°C, and cough and/or sore throat) and have suspected or confirmed evidence of exposure to H1N1 virus. This could include specific exposure to a confirmed case or evidence of H1N1 activity in the community. Novel H1N1 may also be associated with gastrointestinal symptoms such as nausea, vomiting and diarrhea in up to a third of cases. Atypical presentations may occur in those with significant immunosuppression and/or lymphopenia (e.g. fever with no other symptoms or an afebrile patient with rhinorrhea alone).•We recommend confirming a diagnosis by specific testing when H1N1 is suspected in a transplant patient. This includes patients with influenza-like illness and those with milder symptoms such as rhinorrhea if contact with novel H1N1 has occurred.○Suspected cases of H1N1 are defined as those occurring in patients who have signs and symptoms consistent with influenza and potential exposure to H1N1 (i.e. presence of H1N1 activity in the community or exposure within the prior 7 days to a confirmed or probable case) in the absence of another defined cause of symptoms.○Probable cases are patients who have flu-like symptoms, positive testing for influenza A and negative for seasonal H1 and H3 by influenza reverse transcriptase polymerase chain reaction (RT-PCR).○Confirmed cases require confirmation of the presence of novel H1N1 (2009) by real-time RT-PCR or viral culture (9http://www.cdc.gov/h1n1flu/casedef.htmGoogle Scholar).•Appropriate samples for testing include nasopharyngeal swab with or without an oropharyngeal swab, or a nasal aspirate. Endotracheal aspirates from intubated patients, bronchoalveolar lavage specimens and sputum specimens may also be used. All specimens should be promptly placed in sterile viral transport media and kept at 4°C for transport to the microbiology laboratory (10http://www.cdc.gov/h1n1flu/specimencollection.htmGoogle Scholar).•Specific testing for H1N1 by standard methodology should be performed using real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other nucleic acid based detection assay whenever possible. Samples that are positive for influenza A and negative for seasonal H1 and H3 can be further tested at the CDC or state laboratories for definitive confirmation as H1N1.•If RT-PCR is not available, rapid antigen detection may be acceptable for point of care testing, although will have lower sensitivity (estimated to range from 10% to 51%) and will not differentiate novel H1N1 from other strains of influenza A. Consequently, negative rapid tests cannot exclude the diagnosis (11Ginocchio CC Zhang F Manji R et al.Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak.J Clin Virol. 2009; 45: 191-195Crossref PubMed Scopus (310) Google Scholar).•Immunofluorescence by direct or indirect assays can also identify influenza A but will not differentiate novel H1N1 strains from seasonal influenza, In addition, the rapid kits have variable sensitivity for novel H1N1; accordingly, a patient with a negative test must have further testing with more a sensitive method (11Ginocchio CC Zhang F Manji R et al.Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak.J Clin Virol. 2009; 45: 191-195Crossref PubMed Scopus (310) Google Scholar,12http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a2.htmGoogle Scholar).•Specific instructions on collection of appropriate specimens for testing are available at http://www.a-s-t.org/files/pdf/ast_h1n1_guidance.pdf. •The viral dynamics of seasonal influenza have been well studied among hematopoietic stem cell transplant recipients and prolonged viral replication, even in the setting of active antiviral therapy has been shown (13Khanna N Steffen I Studt JD et al.Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation.Transpl Infect Dis. 2009; 11: 100-105Crossref PubMed Scopus (100) Google Scholar). Similar studies have not been conducted in SOT recipients.•Lymphocyte depletion as well as enhanced immune suppression, particularly high doses of steroids, are likely to prolong viral replication (14Nichols WG Guthrie KA Corey L Boeckh M Influenza infections after hematopoietic stem cell transplantation: Risk factors, mortality, and the effect of antiviral therapy.Clin Infect Dis. 2004; 39: 1300-1306Crossref PubMed Scopus (313) Google Scholar). Viral replication of novel influenza A/H1N1 is predicted to be prolonged in transplant recipients.•As such, the optimal duration of therapy for influenza has not been well established but courses longer than the currently approved 5 days may be needed. Some experts recommend continuing antiviral therapy until viral replication has ceased (e.g. check PCR once a week and treat until negative). Duration of therapy should be guided based on current CDC treatment recommendations and individualized patient assessments. Lung transplant patients with impaired lung function may need longer treatment than other organ transplant recipients.•As recommendations on therapy may change over time, consult the CDC antiviral therapy page prior to selecting antiviral therapy http://www.cdc.gov/h1n1flu/recommendations.htm (15http://www.cdc.gov/h1n1flu/recommendations.htmGoogle Scholar).•In healthy individuals, use of antiviral agents has not been found to be beneficial if symptoms have been present for more than 48 h. Contrary to this, there is likely to be benefit in treating symptomatic SOT recipients with evidence of viral replication (positive culture, rapid antigen or PCR-based testing), even if symptoms have extended beyond 48 h. Treatment of all transplant patients is recommended regardless of the duration of symptoms (Table 1).Table 1CDC-recommended doses of oseltamivir and zanamivirDrugTreatment dose1Dose recommended in normal renal function. Some experts recommend of doses of agents the approved as studies demonstrated a antiviral activity with are data on the and of in lung transplant recipients. there is exposure of the The clinical of this is treatment or recommendations are available for patients renal once recommended in normal renal function. Some experts recommend of doses of agents the approved as studies demonstrated a antiviral activity with et and of the oseltamivir in treating acute influenza: A PubMed Scopus Google are data on the and of in lung transplant recipients. there is exposure of the The clinical of this is treatment or recommendations are available for patients renal in a new antiviral therapy should be in SOT recipients in symptoms are of novel influenza A/H1N1 of Novel Influenza All must be made to a diagnosis, has been noted in SOT recipients with novel influenza A/H1N1 (14Nichols WG Guthrie KA Corey L Boeckh M Influenza infections after hematopoietic stem cell transplantation: Risk factors, mortality, and the effect of antiviral therapy.Clin Infect Dis. 2004; 39: 1300-1306Crossref PubMed Scopus (313) Google on treating the who is at the of diagnosis are not available. should be novel H1N1 is to and and this should not be as All novel H1N1 are to all approved and and A of novel H1N1 have been to have developed resistance to oseltamivir secondary to a at over the course of therapy Scholar). strains have to be to of influenza therapy with a and oseltamivir or may be antiviral therapy may be in those who are and have therapy or in there is concern about the of experts recommend that the of oseltamivir may be (e.g. to in adult In patients with significant disease, a in immunosuppression is there are two and has been for for to this is available use and the to an with the with viral replication beyond days active antiviral therapy or of symptoms therapy should the concern for antiviral are laboratories that can resistance testing should include for more than the presence of the there are a of and antiviral that are and/or are available for are and will be updated at http://www.a-s-t.org/files/pdf/ast_h1n1_guidance.pdf. on about resistance, with oseltamivir for the duration of the pandemic is not recommended but can be for may be for transplant recipients, those who have and those in immunization is SOT who has had known exposure to novel Influenza A/H1N1 should be to for signs and symptoms of influenza. A can be treatment doses of and treatment with signs and the transplant patient who has been can to days from the of known exposure doses for children in cases of oseltamivir resistance have in the setting of patients contact with who are known to have been with or of particularly after or should be performed as this is an effective to the of cough the and with a when or and the in the after no is available, the should cough or to for well health and tests to a health care should be during should be when available from health care or health for seasonal influenza and for novel are no for SOT patients with to care should and not have contact with patients if have symptoms of influenza-like programs should with SOT candidates and recipients with to H1N1. of infection control should be at Control for Novel Influenza patients and candidates should be with at of H1N1 more than is to will on the of In healthy a of 2009 H1N1 vaccine had a of GF et after of a influenza A (H1N1) 2009 vaccine – Engl J Med. 2009; 10. [Epub ahead of print].)Crossref Scopus Google Scholar). H1N1 vaccine the had a of after a M K et of influenza A (H1N1) 2009 vaccine – Engl J Med. 2009; 10. [Epub ahead of print].)Crossref Scopus Google recipients, candidates and contacts should also the trivalent influenza vaccine in addition to H1N1 a transplant has already vaccine there is no need to a seasonal influenza vaccine is recommended to be after transplant for vaccination of solid organ transplant candidates and recipients. J Transplant Scholar). the rapid spread of H1N1 transplant recipients can to H1N1 vaccine as as the immune response of vaccination may be the of and with H1N1 vaccine is there is no to that will be than those with the seasonal influenza H1N1 vaccine is available, this should be to SOT recipients. to of to the of vaccination and the of antigen for an effective vaccine is no evidence that the of allograft SOT recipients are a for vaccine should also be updated the of infection in those with care in contact with SOT candidates and recipients should also be with seasonal and novel H1N1 can be in influenza vaccine is a virus vaccine and should not be to SOT who may virus for up to 21 days for Scholar). may be a and of transmission of vaccine virus to transplant recipients from close contacts who influenza health care in contact with transplant recipients, if and are available, vaccine is if vaccine is available, those for transplant recipients should be All health care should be to is for those that have The use of may be as if and are available, vaccine is if vaccine is available, vaccination should be In this the of and contact with (e.g. direct should be to the patient and from a donor who has the can be virus has not been shown to in lung for Scholar). Influenza illness is more likely to present in a in to children and for may present with a In addition, diarrhea may be in influenza illness is present in the of illness among adult is when a with influenza illness to a health care setting, the also have influenza with infection control is in The use of in In addition, children are not likely to be with respiratory Viral may be more prolonged and in children to the SOT patient is to virus for an even more prolonged and be more likely than to spread the virus to close contacts and to the should use for and influenza vaccine is approved for and children than of the of who are seasonal influenza vaccine for the will require two transplant recipients of should also H1N1 All and close contacts of SOT recipients should also be SOT recipients of should be a for the of data on the use of antiviral agents in of transplant recipients to influenza although responses may not be as as that found in healthy children A et of the immune response to influenza vaccine in liver transplant recipients and healthy Infect Dis. 2008; PubMed Scopus Google The to the use of antiviral agents in the treatment and of novel H1N1 influenza in children is to and has been from CDC and other The recommended is shown in 2 and are that should be as recommendations for children of or 5 once once once once use is 7 of 7 or once 7 or use is 7 of in a new recommendations for children than of with oseltamivir 5 with oseltamivir recommended to data on use in this once once are recommended for patients with and patients, the treatment is to a once the is with the other in a new on data from a of experts recommend of oseltamivir for children than particularly for or based on for than of to should should for than of to are recommended for patients with and patients, the treatment is to a once the is with the other et and in from a at Infectious Diseases Society of 2009. Health care should be of the of data on and of oseltamivir in with confirmed 2009 H1N1 infection or following exposure to a confirmed 2009 H1N1 influenza should be for when oseltamivir is used. A infectious disease consult is information on oseltamivir for this can be found was concern the of oseltamivir in than year of This was based on data using that than what be in data are the of evidence to the of oseltamivir in than year of is As such, at this point in time, current the use of oseltamivir in than year of of than year of as data are on appropriate of oseltamivir in this and those with lower most experts based on such are available. In all an infectious diseases must be when antiviral agents are in this is respiratory during or can be on the of who are within to of the respiratory may also to spread when areas and on A on for it may than on such as or can longer on virus may for on human on of Influenza to the August 2009.Google candidates and recipients who present at health care including should be by signs and to identify if have symptoms of influenza-like should be and and should be should be to patients who are and until can be placed in a for influenza cases from other patients is recommended but cannot respiratory viral infection from an SOT to the for influenza-like using and should be This that health care a or and in 2004; August 2009.Google should be placed in with the kept are not available, H1N1 influenza patients may be once the diagnosis has been should be to patients in from the transplant should until or until the signs and symptoms of influenza have and the patient has been afebrile for at h. to the of prolonged viral and symptoms, it is to until if or of a negative test for H1N1 N et and duration of viral in adult patients with Infect Dis. 2009; PubMed Scopus Google with respiratory symptoms should be should be to appropriate when patients, including a and for the of to Control Influenza August 2009.Google Scholar). contacts of the influenza who may be symptoms of influenza, should be for symptoms and to if contacts may be candidates for antiviral with influenza are to before symptoms infectious for 5 days after although immunosuppressed and children may be for or more an influenza all donors and recipients should be for clinical symptoms and signs of flu-like potential organ donor and must be with specific guidance if from infectious disease or clinical with other causes of potential for influenza illness and/or should be transmission has a prolonged not novel H1N1 infection. In should have a to test potential donors and of the rapid tests are sensitive (11Ginocchio CC Zhang F Manji R et al.Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak.J Clin Virol. 2009; 45: 191-195Crossref PubMed Scopus (310) Google and more sensitive testing should be with a sensitivity of over The duration of positive assays days or from the of should be when donors and recipients with flu-like organ donors who have been as having influenza (e.g. within the 2 should likely be from lung and those donors with influenza who have appropriate antiviral therapy could be as potential or organ after from the organ and infectious disease experts also are currently no data on the duration of therapy for the donor before organs can be used. until more data are available many recommend a to course of therapy not for the if the donor not a course of a of cases of peritransplant novel H1N1 infection have organ in the presence of suspected infection should be the potential donor is found to have novel H1N1 transplantation should be if until the donor has a course of treatment and is transmission of influenza is should be made to disease in the donor and recipient. Transplant may to specimens and nasal or nasopharyngeal swab samples for further influenza is and to be donor-derived in other with recipients from the donor should be organ influenza in SOT recipients should be with oseltamivir and/or on the patient and resistance patterns at the of to the recommendations by the CDC and of Novel Influenza resistance, optimal treatment recommendations may over SOT recipients are in of for such patients may to the duration of treatment and antiviral therapy until viral replication has been to be should be for allograft and for or with pneumonia or other In addition, should immunosuppression if although the of rejection in the transplant must be against the of influenza on an and

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.